A growing proportion of U.S. women with HIV infection are from the Southeastern United States. Compared to all other states in the Southern region of the U.S., Florida has the highest number of HIV-infected individuals and the highest rates of HIV transmission. Miami-Dade County has one of the highest rates of new infections among women and the prevalence of HIV among women was among the highest in a national study of 21 epicenter cities in the U.S. Heterosexual transmission and intravenous drug use were the major risk factors for infection. Compounding these issues, Miami-Dade County ranks high among U.S. areas in measures of social and economic distress. The Women's Interagency HIV Study (WIHS) seeks to expand its efforts to better understand the current epidemiology of HIV infection in women with the identification of new sites from the Southern region of the U.S. The Miami WIHS is well positioned to engage women with HIV infection and at risk for HIV infection that are representative of this region and the changing demographics of the HIV epidemic, as well as addressing important current treatment outcomes and the impact of disassociation from care among hard-to-reach populations (e.g. substance abusing individuals). Miami sits at the portal to the Caribbean and Central and South America and, as a result of the high rates of immigration from these regions; the women infected with HIV belong to a wide, diverse population. In addition, the HIV-infected population of women in Miami spans generational boundaries from pediatrics through to the elder. This project is a multiple PI project between the University of Miami Miller School of Medicine and the Columbia University Mailman School of Public Health with collaboration from the University of Florida. We will seek to enroll a diverse cohort of 300 youth, young adult and adult women, including women who are at-risk for HIV, those with limited disease progression, those with newly recognized infection, who are antiretroviral treatment nave and antiretroviral treatment experienced participants, and who are in care, intermittently in care and not in care. A highly experienced and diverse team of researchers has been assembled to ensure the success of this program, including clinical, basic and behavioral/social scientists, with strong ties to th community. The specific aims outlined respond directly to the overall WIHS scientific goals and advance and expand the WIHS basic, clinical and epidemiologic/behavioral/social science research agenda. The proposed scientific agenda taps into the experience and expertise of the Miami WIHS researchers to examine critically important and scientifically rigorous research questions. The proposed research projects will examine the impact of aging on immune functionality; reproductive decision making among young adult and adult women living with HIV/AIDS; increasing viral diversity and the impact of HIV-1 non-B subtype infections on the clinical course of HIV and response to therapy; and the interplay of crack cocaine use and associated co-occurring epidemics (mental health, poverty, unemployment and interpersonal violence with uptake of optimal antiretroviral therapy and engagement and retention in care. By coupling the diverse population base of HIV-infected and at risk women with the recognized strengths in HIV/AIDS research, the Miami WIHS is perfectly situated to advance the overall WIHS scientific agenda of defining clinical outcomes among women across their lifespan, including the uptake of antiretroviral therapy; use and retention of HIV primary care and other ancillary services; treatment outcomes on viral suppression, immune recovery and normalization of the effects of HIV, and disease pathogenesis, as well as, promoting and advancing local scientific research goals.